Thursday, October 29, 2015

JID: Statins & Flu Vaccine Effectiveness

One of the challenges with the flu vaccine is that it is generally less effective for those over the age of 65, which also happens to be the the age cohort at greatest risk from influenza. Several reasons are believed behind this, but prime among them is the fact that our immune responses simply become less robust as we age.

But other factors – including medicines they may be taking – may also affect vaccine effectiveness (VE).

A number of years ago, in A Few Inflammatory Remarks, we looked at several studies that suggested that taking antipyretic medications – like acetaminophen, Aspirin, or other NSAIDs – could reduce the effectiveness of some vaccinations or blunt the level of acquired immunity from actual infection.

This study only looked at low-dose aspirin use, and therefore cannot be automatically assumed to apply to other NSAIDs or antipyretics, or larger doses of aspirin.

But statins are another widely prescribed (40% of those > 65) class of prescription drug with proven anti-inflammatory and immunomodulatory effects, both of which could plausibly impact vaccine effectiveness. Previously, and for the very same reasons, we’ve seen statins suggested as a possible treatment for pneumonia, pandemic influenza, and even MERS.

While the theory behind the use of statins to treat these, and other inflammatory response producing illnesses, is reasonable – results from very limited real-world studies have thus far been mixed.

Overnight the Journal of Infectious Diseases released two studies, and a commentary, on the possible effect of statins on flu vaccine effectiveness. I say `possible’, because these are preliminary studies, will require further research to confirm, and are by no means the final word on the subject.

A new pair of studies suggests that statins, drugs widely used to reduce cholesterol, may have a detrimental effect on the immune response to influenza vaccine and the vaccine's effectiveness at preventing serious illness in older adults. Published in The Journal of Infectious Diseases, the findings, if confirmed by additional research, may have implications for flu vaccine recommendations, guidelines for statin use around the time of vaccination, and future vaccine clinical trials in seniors.

In one of the new studies, researchers analyzed immune response data from an earlier flu vaccine clinical trial conducted during the 2009-2010 and 2010-2011 flu seasons. In the new study, funded by Novartis Vaccines, which also sponsored the original clinical trial, investigators focused on the potential effect of statin use on patients' initial immune responses after being immunized against flu. The analysis drew on data for nearly 7,000 adults over the age 65 in four countries, including the United States.

Statin users had a significantly reduced immune response to vaccination compared to those not taking statins, as measured by the level of antibodies to the flu vaccine strains in patients' blood three weeks after being vaccinated, the researchers observed. The effect was most dramatic in patients on synthetic statins, rather than naturally derived statins.

(SNIP)

The results from both new studies are biologically plausible and raise important questions, but the findings should not yet affect how physicians care for their patients, according to a related editorial commentary by Robert L. Atmar, MD, and Wendy A. Keitel, MD, of Baylor College of Medicine in Houston.

"Instead, the results of these studies should be viewed as hypothesis-generating and should prompt further investigations into whether statins reduce inactivated influenza vaccine immunogenicity and, if so, the mechanisms by which immune responses and associated vaccine effectiveness are adversely affected," the commentary authors wrote. The commentary accompanies the two studies in The Journal of Infectious Diseases.

Fast Facts

Statins are used by more than 40 percent of the U.S. population over the age of 65, according to the Centers of Disease Control and Prevention.

In one study of flu vaccine recipients older than 65, statin users had a significantly reduced immune response to flu vaccination, compared to those not taking statins.

In another study, vaccine effectiveness at preventing serious respiratory illness was lower among patients taking statins compared to patients who were not on statins.

Additional research is needed to confirm the findings from both studies before potential changes in clinical practice are warranted.

The three articles may be accessed at:

Influence of Statins on Influenza Vaccine Response in Elderly Individuals

The authors advise - If confirmed - these findings could support the preferential use of high-dose flu vaccine or vaccines containing adjuvants to boost immune response in the elderly.

For those over 65 taking statins, there is a High-Dose flu vaccine option currently available that contains 4 times the normal amount of antigen; 60 µg of each of the three recommended strains, instead of the normal 15 µg (see MMWR On High Dose Flu Vaccine For Seniors).

Does the higher dose vaccine produce a better immune response in adults 65 years and older?

Data from clinical trials comparing Fluzone to Fluzone High-Dose among persons aged 65 years or older indicate that a stronger immune response (i.e., higher antibody levels) occurs after vaccination with Fluzone High-Dose. Whether or not the improved immune response leads to greater protection has been the topic on ongoing research. A study published in the New England Journal of Medicine indicated that the high-dose vaccine was 24.2% more effective in preventing flu in adults 65 years of age and older relative to a standard-dose vaccine. The confidence interval for this result was 9.7% to 36.5%).

Additionally, work continues on improving overall vaccine effectiveness, including research on adjuvants – not currently approved in the United States but widely used in Europe – to boost the immune response.